Lyme disease is the most common vector-borne disease in the United States. It is caused by the transmission of the bacterium, Borrelia Burgdorferi (Bb), through an infected Ixodes Scapularis' (black-legged tick) bite. Lyme disease is difficult to diagnose in its early stages and if not treated promptly, it can lead to severe, lifelong complications. This challenge has led to a reliance on preventative measures limited to applying insect repellent, removing ticks promptly, applying pesticides to the environment, and reducing tick habitat. Unlike these current preventative measures that depend on constant vigilance against the vector, a vaccine would reduce transmission risk and provide reliable, long-term protection against Lyme disease. Outer membrane vesicles (OMVs), nanoparticles produced by gram-negative bacteria, may represent a promising new vaccine platform. OMVs structurally resemble bacterial surfaces, making them highly immunogenic, but they are unable to replicate and pose limited threat to the body. Beyond their natural immunogenicity, OMVs can be bioengineered to generate fusion proteins, enabling them to carry various antigens. Fusion proteins expressed on the exterior of OMVs allow the antigenic component to be directly exposed to the immune system, eliciting an antigen-specific immune response.
My research focused on evaluating different fusion proteins on the surface of OMVs. These fusion proteins each consist of a protein anchoring system, Bb-based antigenic epitopes (a small part of a protein that is recognized by the immune system), and a his-tag (for identification purposes). Specifically, Cytolysin A (ClyA) and Hemoglobin protease (Hbp) were evaluated as protein anchoring systems, and the proteins tested were Decorin-binding protein A (DbpA) and RevA epitopes. Through BCA Assay, western blot analysis, dynamic light scattering, and the protease accessibility assay, three types of Lyme protein OMVs were shown to be consistently produced with tested fusion proteins on their outer surface, indicating that the antigenic component will be directly exposed to the immune system and eliciting a strong immune response in vivo. All three of these engineered OMVs are promising candidates for future vaccine formulations.
Acknowledgements: National Science Foundation, NSF-ERI: "Evaluation of the Immune Response to Lyme Disease Antigens Using Bacterially-Derived Outer Membrane Vesicles" (CBET 2347479)